Pharmacologically active compounds



United htates Patent fitice 3,028,378 Patented Apr. 3, 1962 3,628,378PHARWACOLOGICALLY ACTIVE COIVHOUNBS Emilio Testa, Vacallo, Ticino,Switzerland, and Luigi Fontanella and Giulio Mallii, Milan, Italy,assignors to Lepetit S.p.A., Milan, Italy No Drawing. Filed Dec. 18,1959, Ser. No. 860,313 Claims priority, application Great Britain Dec.23, 1958 6 Claims. (Cl. 260-239) This invention is concerned with newpharmacologically active compounds. More particularly the invention isconcerned with 3-substituted l-hydroxyalkylazetidines and their acylderivatives of the formula wherein R represents hydrogen, lower alkyl,cycloalkyl, aryl and aralkyl radicals, R represents lower akyl,cycloalkyl, aryl or aralkyl radicals and R represents hydrogen or anacyl radical.

The compounds of the invention have been found to possess a considerablehypotensive activity.

The process of the invention consists in reacting a 3-substitutedazetidine of the formula R CH;

wherein R and R have the above significance, with ethylene oxide in aninert anhydrous organic solvent at room temperature, and if desiredacylating the formed N-hydroxyethylazetidine by conventional methods.

The starting materials, i.e., 3-substituted azetidines, are

I prepared by bringing together a 2-azetidinone of the formula:

3-phenyl-3-ethyl-1-(B-hydroxyethyl) azetidine.-To a solution of 30 g. ofethylene oxide in 250 ml. of anhydrous ethanol, a solution of 100 g. of3-phenyl-3- ethylazetidine in 50 ml. of anhydrous ethanol is slowlyadded with stirring. After 3 days at room temperature the solvent isremoved and the residue distilled. B.P. 100-105/0.4 mm; yield g. (72%).

Example 2 3,3-diethyl-1 (5-hydr0xyethyl)-azetialine.--To a solution of30 g. of ethylene oxide in 250 ml. of anhydrous ethanol, a solution of70 g. of 3,3-diethylazetidine in ml. of anhydrous ethanol is slowlyadded with stirring. After 2 days at room temperature the solvent isremoved and the residue distilled. B.P. 73-75 0.6-0.8 mm; yield 80 g.(82%).

Example 3 3-plzenyl-3-ethyl-1-(B-benzoyloxymethyl) azetz'dine.- To asolution of 41.5 g. of 3-phenyl-3-ethyl-l-(fi-hydroxyethyl)-azetidine,14 g. of benzoyl chloride are slowly added with stirring. After additionof water, the mixture is neutralized with sodium carbonate and extractedwith diethyl ether. The solvent is then removed and the residuedistilled. Yield 55 g. (87%); B.P. l60-l70/ 0.3

Example 4 3-phenyl-3-methyl-1 (Q hydroxyethyl)-azetidine.- Thiscompound, prepared according to the process of Example 1 has B.P.lO71l0/0.1 mm.; yield 68%.

Example 5 3-phenyl-3-n-pr0pyl-1-(}3-hydroxyethyl) azetidine.- Preparedas described in Example 1. B.P. ll0-120/ 0.2 mm.; yield 79%.

Examples 6 to 9 According to the process of Example 1 the followingl-(fl-hydroxyethyl)-azetidines are prepared. Yields (y.) and boilingpoints (B.P.) are given.

3-phenyl-3 -isopropyl y. 77%, B.P. 1l0-120/O.2-0.4 mm. 3,3-dimethyl y.68%, B.P. 80-83/2224 mm. 3-pheny1-3-nbutyl y. 88%, B.P. 125-130/0.30.5mm. 3-phenyl y. 74%, B.P. -110/0.8 mm.

We claim:

1. A compound of the formula wherein R is selected from the classconsisting of hydrogen, lower alkyl, and phenyl, R is selected from theclass consisting of lower alkyl and phenyl, and R is selected from theclass consisting of hydrogen and benzoyl.

2. 3-phenyl-3-ethyl-1-(fi-hydroxyethyl)-azetidine.

3. 3,3-diethyl-1-(B-hydroxyethyl)-azetidine.

4. 3-phenyl-3-ethyl-l-(fi-benzoyloxyethyl -azetidine.

5. 3-phenyl-3-n-propy1-I-(B-hydroxyethyl)-azetidine.

6. 3-phenyl-1-(B-l1ydroxyethyl)-azetidine References Cited in the fileof this patent Chemical Abstracts, vol. 33, p. 4197 (1939).

Funke et a1.: Bull. Soc. Chim. France, (1953), pp. 1021-23.

1. A COMPOUND OF THE FORMULA